Osteoporosis is a common condition that presently affects more than 25 million persons in the US, contributing to over 1.5 million fractures annually. The economic and social impact of these fractures on health care delivery and on the elderly population are staggering. Furthermore, if current trends continue, the number of fractures and associated costs are projected to double or triple in the next 30 years due to the aging of our population. Early identification, through widespread screening programs, and intervention in those persons at high risk may improve the success of fracture prevention strategies. The most commonly used technique for assessing fracture risk, dual-energy x-ray absorptiometry (DXA), though proven effective as a predictor of future fracture risk, may not be the ideal screening tool due to the relatively high capital investment required, the need for specialized operator training, and limited portability. Recently, alternatives to DXA have been developed. We propose studies designed to further our basic understanding and to evaluate the potential usefulness of two of these alternative methods: image analysis of conventional radiographs and quantitative ultrasound (QUS). In the first two aims we will evaluate a diagnostic technique based on image processing of conventional forearm radiographs. In this technique, a bone index representing the character of the projected trabecular pattern is computed from standard radiographs. We will compare this bone index to the strength of cadaveric femurs and thoracolumbar vertebrae, and assess its ability to predict hip fracture risk in case-control study of women with an acute hip fracture and similarly-aged women who have not suffered a fracture. In our final aim, we will examine the capabilities of QUS. It has been proposed that QUS measures aspects of bone "quality", such as trabecular architecture, material properties, or accumulated microdamage, that are independent of bone density. However there have been few studies relating QUS measurements on intact feet (rather than excised bone specimens) to aspects of bone quality. We will use human cadaveric specimens to characterize the relationship between QUS measurements of on intact feet and trabecular bone morphology, mechanical properties, and microdamage. The significance of the proposed work is that is will provide new information regarding the potential usefulness of two technologies that may be capable of widespread osteoporosis testing and assessment of fracture risk. This information is important, as early identification of those at risk for fracture represents the most promising approach for effective fracture prevention.